Somatic mutation detection from liquid biopsy-derived cellular aggregates formed by magnetic 3D bioprinting


There is increasing interest in the analysis of circulating tumor cells (CTC) from liquid biopsies to track dynamic changes in mutational profile. One of the major challenges to CTC analysis is the inability to culture them, largely due to their scarcity preventing their survival in culture. CTC culture would allow for their expansion, analysis, and the potential development of companion in vitro diagnostics and novel therapies. Towards that end, we use a novel technique, magnetic 3D bioprinting, to culture CTCs into spheroids. The principle behind magnetic 3D bioprinting is the magnetization of cells and their aggregation into spheroids using magnetic forces.1,2 We can use this method to actively magnetize CTCs, then aggregate them into close contact for their survival, expansion, and analysis. Magnetization is accomplished via incubation with NanoShuttleTM, a biocompatible nanoparticle assembly that is non-specific, and does not interfere with fluorescence or require specialized equipment. In this study, we demonstrated the ability to aggregate CTCs using magnetic 3D bioprinting, then perform next generation sequencing (NGS) to detect somatic mutations from renal and prostate cancers.